1. Field of the Invention
The present invention relates to a new process for the preparation of antitumor glycosides including the known antibiotics daunomycin and adriamycin. The process is based on the reaction between protected glycals and anthracyclinones or reactive protected derivatives thereof to produce substituted 2-deoxv-glycosides, which, after removal of the protecting groups are converted to antitumor compounds effective in the treatment of certain forms of human cancer and leukemia, such as sarcomas, breast cancer, bronchogenic carcinoma, malignant lymphomas, neuroblastomas, acute leukemia and bladder cancer.
2. Prior Art
Glycoside antibiotics are known. For example, daunomycin and its aglycone, daunomycinone are well known compounds. They are described and claimed in British Pat. No. 1,003,383. Adriamycin and its aglycone, adriamycinone are also well known compounds, being described and claimed in British Pat. No. 1,161,278; both such British patents being owned by the unrecorded assignee hereof.
The above glycoside antibiotics are prepared according to the processes disclosed in the Arcamone et al applications incorporated herein by reference by reacting the aglycone, or a reactive derivative thereof with a reactive protected derivative of the pyranose sugars daunosamine and 4'-epidaunosamine.
The present invention utilizes a novel, reactive, protected derivative of a 1,2-unsaturated pyranoid sugar. These compounds are known generically as "glycals". See, for example, the monograph entitled "Unsaturated Sugar, Advances in Carbohydrate Chemistry", Vol. 20, page 67 (1965, Academic Press, London). In this monograph a number of glycals including D-arabinal (3,4-di-O-acetyl); L-arabinal (3,4-di-O-acetyl); D-allal(4,6-O-benzylidene); D-glucal(4-deoxy); L-glucal(3,4-di-O-acetyl), etc., are described.